This application is directed to an improved process for making 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami de. A general process is disclosed in U.S. Pat. No. 5,466,823 and Penning et al., J. Med. Chem., Vol. 40, pp. 1347-1365, 1997. The process described herein yields a product with a higher ratio of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami de with respect to its regioisomer, a higher yield and greater degree of purity than the previously disclosed process. The compound is generally useful as a non-steroidal antiinflammatory agent.
Non-steroidal, antiinflammatory drugs (NSAIDs) exert most of their antiinflammatory, analgesic and antipyretic through an inhibition of prostaglandin G/H synthase, also known as cyclooxygenase. Initially, only one form of cyclooxygenase was known, this corresponding to cyclooxygenase-1 (COX-1) or the constitutive enzyme. More recently, a second inducible form of cyclooxygenase, COX-2, has been characterized. This enzyme is distinct from the COX-1 enzyme. COX-2 is rapidly and readily inducible by a number of agents including mitogens, endotoxin, hormones, cytokines and growth factors. The constitutive enzyme, COX-1, is responsible in large part for endogenous basal release of prostaglandins and hence is important in physiological functions, such as the maintenance of gastrointestinal integrity and renal blood flow. In contrast, COX-2, is mainly responsible for the pathological effects of prostaglandins where rapid induction of the enzyme would occur in response to such agents as inflammatory agents, hormones, growth factors, and cytokines.
A brief description of the potential utility of cyclooxygenase-2 inhibitors is given in an article by John Vane, Nature, Vol. 367, pp. 215-216, 1994, and in an article in Drug News and Perspectives, Vol. 7, pp. 501-512, 1994.
Thus, one object of the present invention is to provide a process that yields a product with a higher ratio of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonami de with respect to its regioisomer.
Another object of the present invention is to provide a process with a higher yield and greater degree of purity. These and other objects will be apparent to those of ordinary skill from the teachings contained herein.